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Isabelle M. Maisonneuve - One of the best experts on this subject based on the ideXlab platform.
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Brain regions mediating α3β4 nicotinic antagonist effects of 18-MC on methamphetamine and sucrose Self-Administration
European Journal of Pharmacology, 2008Co-Authors: Stanley D. Glick, Elizabeth M Sell, Isabelle M. MaisonneuveAbstract:The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the Self-Administration of several drugs of abuse. Previous work has established that 18-MC is a potent antagonist at α3β4 nicotinic receptors. Because high densities of α3β4 nicotinic receptors occur in the medial habenula and the interpeduncular nucleus and moderate densities occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, the present study was conducted to determine if 18-MC could act in these brain areas to modulate methamphetamine Self-Administration in rats. Local administration of 18-MC into either the medial habenula, the interpeduncular area or the basolateral amygdala decreased methamphetamine Self-Administration. Similar results were produced by local administration into the same brain areas of two other α3β4 nicotinic antagonists, mecamylamine and α-conotoxin AuIB. Local administration of 18-MC, or the other antagonists, into the dorsolateral tegmentum or the ventral tegmental area had no effect on methamphetamine Self-Administration. In contrast, local administration of 18-MC and the other antagonists decreased sucrose Self-Administration when administered into the dorsolateral tegmentum or basolateral amygdala but had no effect when infused into the medial habenula, interpeduncular nucleus, or ventral tegmental area. These data are consistent with the hypothesis that 18-MC decreases methamphetamine Self-Administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of α3β4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala. The data also suggest that the basolateral amygdala along with a different pathway involving α3β4 receptors in the dorsolateral tegmentum mediate the effect of 18-MC on sucrose Self-Administration.
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Brain regions mediating alpha3beta4 nicotinic antagonist effects of 18-MC on methamphetamine and sucrose Self-Administration.
European journal of pharmacology, 2008Co-Authors: Stanley D. Glick, Elizabeth M Sell, Isabelle M. MaisonneuveAbstract:The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the Self-Administration of several drugs of abuse. Previous work has established that 18-MC is a potent antagonist at alpha3beta4 nicotinic receptors. Because high densities of alpha3beta4 nicotinic receptors occur in the medial habenula and the interpeduncular nucleus and moderate densities occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, the present study was conducted to determine if 18-MC could act in these brain areas to modulate methamphetamine Self-Administration in rats. Local administration of 18-MC into either the medial habenula, the interpeduncular area or the basolateral amygdala decreased methamphetamine Self-Administration. Similar results were produced by local administration into the same brain areas of two other alpha3beta4 nicotinic antagonists, mecamylamine and alpha-conotoxin AuIB. Local administration of 18-MC, or the other antagonists, into the dorsolateral tegmentum or the ventral tegmental area had no effect on methamphetamine Self-Administration. In contrast, local administration of 18-MC and the other antagonists decreased sucrose Self-Administration when administered into the dorsolateral tegmentum or basolateral amygdala but had no effect when infused into the medial habenula, interpeduncular nucleus, or ventral tegmental area. These data are consistent with the hypothesis that 18-MC decreases methamphetamine Self-Administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of alpha3beta4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala. The data also suggest that the basolateral amygdala along with a different pathway involving alpha3beta4 receptors in the dorsolateral tegmentum mediate the effect of 18-MC on sucrose Self-Administration.
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18 methoxycoronaridine acts in the medial habenula and or interpeduncular nucleus to decrease morphine self administration in rats
European Journal of Pharmacology, 2006Co-Authors: Stanley D. Glick, Ruby L Ramirez, Jacklyn M Livi, Isabelle M. MaisonneuveAbstract:Abstract The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the Self-Administration of morphine and other drugs of abuse. Previous work has established that 18-MC is a potent antagonist at α3β4 nicotinic receptors. Because α3β4 nicotinic receptors in the brain are preferentially located in the medial habenula and the interpeduncular nucleus, the present study was conducted to determine if 18-MC could act in these brain areas to modulate morphine Self-Administration in rats. Local administration of 18-MC into either the medial habenula or the interpeduncular area decreased morphine Self-Administration while having no effect on responding for a non-drug reinforcer (sucrose). Similar results were produced by local administration into the same brain areas of two other α3β4 nicotinic antagonists, mecamylamine and α-conotoxin AuIB. Local administration of 18-MC into the ventral tegmental area had no effect on morphine Self-Administration. These and other data are consistent with the hypothesis that 18-MC decreases morphine Self-Administration by blocking α3β4 nicotinic receptors in the habenulo-interpeduncular pathway.
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18-Methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus to decrease morphine Self-Administration in rats
European Journal of Pharmacology, 2006Co-Authors: Stanley D. Glick, Ruby L Ramirez, Jacklyn M Livi, Isabelle M. MaisonneuveAbstract:Abstract The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the Self-Administration of morphine and other drugs of abuse. Previous work has established that 18-MC is a potent antagonist at α3β4 nicotinic receptors. Because α3β4 nicotinic receptors in the brain are preferentially located in the medial habenula and the interpeduncular nucleus, the present study was conducted to determine if 18-MC could act in these brain areas to modulate morphine Self-Administration in rats. Local administration of 18-MC into either the medial habenula or the interpeduncular area decreased morphine Self-Administration while having no effect on responding for a non-drug reinforcer (sucrose). Similar results were produced by local administration into the same brain areas of two other α3β4 nicotinic antagonists, mecamylamine and α-conotoxin AuIB. Local administration of 18-MC into the ventral tegmental area had no effect on morphine Self-Administration. These and other data are consistent with the hypothesis that 18-MC decreases morphine Self-Administration by blocking α3β4 nicotinic receptors in the habenulo-interpeduncular pathway.
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18-Methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus to decrease morphine Self-Administration in rats.
European journal of pharmacology, 2006Co-Authors: Stanley D. Glick, Ruby L Ramirez, Jacklyn M Livi, Isabelle M. MaisonneuveAbstract:The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the Self-Administration of morphine and other drugs of abuse. Previous work has established that 18-MC is a potent antagonist at alpha3beta4 nicotinic receptors. Because alpha3beta4 nicotinic receptors in the brain are preferentially located in the medial habenula and the interpeduncular nucleus, the present study was conducted to determine if 18-MC could act in these brain areas to modulate morphine Self-Administration in rats. Local administration of 18-MC into either the medial habenula or the interpeduncular area decreased morphine Self-Administration while having no effect on responding for a non-drug reinforcer (sucrose). Similar results were produced by local administration into the same brain areas of two other alpha3beta4 nicotinic antagonists, mecamylamine and alpha-conotoxin AuIB. Local administration of 18-MC into the ventral tegmental area had no effect on morphine Self-Administration. These and other data are consistent with the hypothesis that 18-MC decreases morphine Self-Administration by blocking alpha3beta4 nicotinic receptors in the habenulo-interpeduncular pathway.
Stanley D. Glick - One of the best experts on this subject based on the ideXlab platform.
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Brain regions mediating α3β4 nicotinic antagonist effects of 18-MC on methamphetamine and sucrose Self-Administration
European Journal of Pharmacology, 2008Co-Authors: Stanley D. Glick, Elizabeth M Sell, Isabelle M. MaisonneuveAbstract:The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the Self-Administration of several drugs of abuse. Previous work has established that 18-MC is a potent antagonist at α3β4 nicotinic receptors. Because high densities of α3β4 nicotinic receptors occur in the medial habenula and the interpeduncular nucleus and moderate densities occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, the present study was conducted to determine if 18-MC could act in these brain areas to modulate methamphetamine Self-Administration in rats. Local administration of 18-MC into either the medial habenula, the interpeduncular area or the basolateral amygdala decreased methamphetamine Self-Administration. Similar results were produced by local administration into the same brain areas of two other α3β4 nicotinic antagonists, mecamylamine and α-conotoxin AuIB. Local administration of 18-MC, or the other antagonists, into the dorsolateral tegmentum or the ventral tegmental area had no effect on methamphetamine Self-Administration. In contrast, local administration of 18-MC and the other antagonists decreased sucrose Self-Administration when administered into the dorsolateral tegmentum or basolateral amygdala but had no effect when infused into the medial habenula, interpeduncular nucleus, or ventral tegmental area. These data are consistent with the hypothesis that 18-MC decreases methamphetamine Self-Administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of α3β4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala. The data also suggest that the basolateral amygdala along with a different pathway involving α3β4 receptors in the dorsolateral tegmentum mediate the effect of 18-MC on sucrose Self-Administration.
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Brain regions mediating alpha3beta4 nicotinic antagonist effects of 18-MC on methamphetamine and sucrose Self-Administration.
European journal of pharmacology, 2008Co-Authors: Stanley D. Glick, Elizabeth M Sell, Isabelle M. MaisonneuveAbstract:The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the Self-Administration of several drugs of abuse. Previous work has established that 18-MC is a potent antagonist at alpha3beta4 nicotinic receptors. Because high densities of alpha3beta4 nicotinic receptors occur in the medial habenula and the interpeduncular nucleus and moderate densities occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, the present study was conducted to determine if 18-MC could act in these brain areas to modulate methamphetamine Self-Administration in rats. Local administration of 18-MC into either the medial habenula, the interpeduncular area or the basolateral amygdala decreased methamphetamine Self-Administration. Similar results were produced by local administration into the same brain areas of two other alpha3beta4 nicotinic antagonists, mecamylamine and alpha-conotoxin AuIB. Local administration of 18-MC, or the other antagonists, into the dorsolateral tegmentum or the ventral tegmental area had no effect on methamphetamine Self-Administration. In contrast, local administration of 18-MC and the other antagonists decreased sucrose Self-Administration when administered into the dorsolateral tegmentum or basolateral amygdala but had no effect when infused into the medial habenula, interpeduncular nucleus, or ventral tegmental area. These data are consistent with the hypothesis that 18-MC decreases methamphetamine Self-Administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of alpha3beta4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala. The data also suggest that the basolateral amygdala along with a different pathway involving alpha3beta4 receptors in the dorsolateral tegmentum mediate the effect of 18-MC on sucrose Self-Administration.
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18 methoxycoronaridine acts in the medial habenula and or interpeduncular nucleus to decrease morphine self administration in rats
European Journal of Pharmacology, 2006Co-Authors: Stanley D. Glick, Ruby L Ramirez, Jacklyn M Livi, Isabelle M. MaisonneuveAbstract:Abstract The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the Self-Administration of morphine and other drugs of abuse. Previous work has established that 18-MC is a potent antagonist at α3β4 nicotinic receptors. Because α3β4 nicotinic receptors in the brain are preferentially located in the medial habenula and the interpeduncular nucleus, the present study was conducted to determine if 18-MC could act in these brain areas to modulate morphine Self-Administration in rats. Local administration of 18-MC into either the medial habenula or the interpeduncular area decreased morphine Self-Administration while having no effect on responding for a non-drug reinforcer (sucrose). Similar results were produced by local administration into the same brain areas of two other α3β4 nicotinic antagonists, mecamylamine and α-conotoxin AuIB. Local administration of 18-MC into the ventral tegmental area had no effect on morphine Self-Administration. These and other data are consistent with the hypothesis that 18-MC decreases morphine Self-Administration by blocking α3β4 nicotinic receptors in the habenulo-interpeduncular pathway.
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18-Methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus to decrease morphine Self-Administration in rats
European Journal of Pharmacology, 2006Co-Authors: Stanley D. Glick, Ruby L Ramirez, Jacklyn M Livi, Isabelle M. MaisonneuveAbstract:Abstract The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the Self-Administration of morphine and other drugs of abuse. Previous work has established that 18-MC is a potent antagonist at α3β4 nicotinic receptors. Because α3β4 nicotinic receptors in the brain are preferentially located in the medial habenula and the interpeduncular nucleus, the present study was conducted to determine if 18-MC could act in these brain areas to modulate morphine Self-Administration in rats. Local administration of 18-MC into either the medial habenula or the interpeduncular area decreased morphine Self-Administration while having no effect on responding for a non-drug reinforcer (sucrose). Similar results were produced by local administration into the same brain areas of two other α3β4 nicotinic antagonists, mecamylamine and α-conotoxin AuIB. Local administration of 18-MC into the ventral tegmental area had no effect on morphine Self-Administration. These and other data are consistent with the hypothesis that 18-MC decreases morphine Self-Administration by blocking α3β4 nicotinic receptors in the habenulo-interpeduncular pathway.
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18-Methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus to decrease morphine Self-Administration in rats.
European journal of pharmacology, 2006Co-Authors: Stanley D. Glick, Ruby L Ramirez, Jacklyn M Livi, Isabelle M. MaisonneuveAbstract:The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the Self-Administration of morphine and other drugs of abuse. Previous work has established that 18-MC is a potent antagonist at alpha3beta4 nicotinic receptors. Because alpha3beta4 nicotinic receptors in the brain are preferentially located in the medial habenula and the interpeduncular nucleus, the present study was conducted to determine if 18-MC could act in these brain areas to modulate morphine Self-Administration in rats. Local administration of 18-MC into either the medial habenula or the interpeduncular area decreased morphine Self-Administration while having no effect on responding for a non-drug reinforcer (sucrose). Similar results were produced by local administration into the same brain areas of two other alpha3beta4 nicotinic antagonists, mecamylamine and alpha-conotoxin AuIB. Local administration of 18-MC into the ventral tegmental area had no effect on morphine Self-Administration. These and other data are consistent with the hypothesis that 18-MC decreases morphine Self-Administration by blocking alpha3beta4 nicotinic receptors in the habenulo-interpeduncular pathway.
Edward D. Levin - One of the best experts on this subject based on the ideXlab platform.
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Dextromethorphan and bupropion reduces high level remifentanil Self-Administration in rats.
Pharmacology biochemistry and behavior, 2020Co-Authors: Graham Blair, Corinne Wells, Amir H. Rezvani, John Modarres, Caroline Pace, James M. Davis, Jed E. Rose, Edward D. LevinAbstract:Abstract Opiate addiction has risen substantially during the past decade. New treatments to combat opiate addiction are sorely needed. The current study was conducted to determine the acute individual and interactive effects of bupropion and dextromethorphan in a rat model of opiate Self-Administration using the short-acting synthetic opioid remifentanil. Both of these drugs have been found to reduce Self-Administration of nicotine. Bupropion and dextromethorphan and their combination had differential effects depending on whether the rats showed higher or lower baseline remifentanil Self-Administration. The rats with higher initial remifentanil Self-Administration showed a significant decrease in remifentanil Self-Administration with bupropion or dextromethorphan treatment, compared to the vehicle control condition. This decrease in self-remifentanil administration was most pronounced when combination of the higher doses of bupropion and dextromethorphan were administered. In contrast, the rats with lower baseline remifentanil Self-Administration showed the opposite effect of drug treatment with an increase in remifentanil Self-Administration with bupropion treatment compared to the vehicle control condition. Dextromethorphan had no significant effect inthis group. This study shows that combination bupropion and dextromethorphan affects remifentanil Self-Administration in a complex fashion with differential effects on low and high baseline responders. In subjects with high baseline remifentanil Self-Administration, bupropion and dextromethorphan treatment significantly reduced Self-Administration, whereas in subjects with low baseline remifentanil Self-Administration, bupropion increased remifentanil Self-Administration and dextromethorphan had no discernible effect. This finding suggests that combination bupropion-dextromethorphan should be tested in humans, with a focus on treating people with high-level opiate use.
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Amitifadine, a triple reuptake inhibitor, reduces Self-Administration of the opiate remifentanil in rats
Psychopharmacology, 2020Co-Authors: Edward D. Levin, Corinne Wells, Graham Blair, John Modarres, Caroline Pace, Andrew Hawkey, Zade Holloway, Alexander Vierling, Ashley Ko, Anthony MckinneyAbstract:Rationale A variety of neural systems are involved in drug addiction, and some of these systems are shared across different addictive drugs. We have found several different types of drug treatments that successfully reduce nicotine Self-Administration. Objectives The current set of studies is the first in a series to determine if drug treatments that have been found to significantly reduce nicotine Self-Administration would reduce opiate Self-Administration. Methods Amitifadine, a triple reuptake inhibitor of dopamine, norepinephrine, and serotonin, was assessed in female Sprague-Dawley rats to determine whether it significantly reduces remifentanil Self-Administration with either acute or chronic treatment. Results Acutely, amitifadine doses of 5, 10, and 20 mg/kg each significantly reduced remifentanil Self-Administration. In a chronic study, repeated treatment with 10 mg/kg of amitifadine continued to reduce remifentanil Self-Administration, even after the cessation of treatment. However, amitifadine was not found to attenuate the rise in remifentanil Self-Administration with continued access. This study and our earlier one showed that the 10 mg/kg amitifadine dose did not significantly affect food motivated responding. Amitifadine did not attenuate remifentanil-induced antinociception as measured on the hot plate test but extended and maintained antinociceptive effects. Conclusions These studies show the promise of amitifadine as a treatment for countering opiate Self-Administration for adjunctive use with opioids for analgesia. Further studies are needed to determine the possible efficacy of amitifadine for combating opiate addiction or preventing it in humans during adjunctive use with opioids for chronic pain.
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Chronic memantine decreases nicotine Self-Administration in rats.
European journal of pharmacology, 2019Co-Authors: Edward D. Levin, Corinne Wells, Jed E. Rose, Leah Yao, Wendi Guo, Anica Nangia, Sarah Howard, Erica Pippen, Andrew B. Hawkey, Amir H. RezvaniAbstract:Neurobehavioral bases of tobacco addiction and nicotine reinforcement are complex, involving more than only nicotinic cholinergic or dopaminergic systems. Memantine is an NMDA glutamate antagonist used to improve cognitive function in people with Alzheimer's disease. Glutamate may be an important component of the reinforcing effects of nicotine, so memantine was evaluated as a potential smoking cessation aid. Two studies were conducted with adult female rats, one testing acute effects of memantine over a range of doses for changing nicotine Self-Administration and the other testing the chronic effects of memantine to reduce nicotine Self-Administration. Acute memantine injections slightly, but significantly, increased nicotine Self-Administration in a dose-related manner. In contrast, chronic memantine treatment significantly reduced nicotine Self-Administration. During the first day of memantine administration in the chronic study, nicotine Self-Administration was significantly elevated replicating the acute study. Starting in the second week of treatment there was a significant reduction of nicotine Self-Administration relative to controls. This was seen because memantine treatment prevented the increase in nicotine Self-Administration shown by controls. There even continued to be a memantine-induced lowered nicotine Self-Administration during the week after the cessation of memantine treatment. Memantine or other drugs affecting NMDA glutamate receptors may be useful aids to smoking cessation. Full efficacy for reducing nicotine Self-Administration was seen as the NMDA drug treatment is given chronically. Importantly, the effect persisted even after treatment is ended, indicating the high potential for NMDA glutamate receptors to impact nicotine addiction.
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Prolonging the Reduction of Nicotine Self-Administration in Rats by Coadministering Chronic Nicotine With Amitifadine, a Triple Monoamine Reuptake Inhibitor With CYP2B6 Inhibitory Actions.
Nicotine & Tobacco Research, 2019Co-Authors: Edward D. Levin, Susan Slade, Corinne Wells, Jed E. Rose, Anthony A Mckinney, Amir H. RezvaniAbstract:INTRODUCTION: Existing treatments can aid tobacco smoking cessation, but they have low efficacy. Because there is a network of neural systems involved in tobacco addiction, combination treatments may provide greater efficacy. Chronic nicotine and amitifadine have each been shown to significantly reduce nicotine Self-Administration in rats. This study was conducted to determine if the combination of chronic nicotine with amitifadine, a triple monoamine reuptake inhibitor with CYP2B inhibitory effects, would reduce nicotine Self-Administration to a greater extent than either alone or placebo. METHODS: This study tested the combination of nicotine plus amitifadine in young adult female Sprague-Dawley rats self-administering nicotine (0.03 mg/kg/infusion). This combination was compared with each treatment alone and the vehicle during continuing nicotine Self-Administration as well as during resumption of Self-Administration after a week of enforced abstinence, modeling a quit attempt. Finally, we studied the residual effects of these therapies after discontinuation of treatment. RESULTS: Treatment with either chronic nicotine or amitifadine alone significantly reduced nicotine Self-Administration relative to controls. The combination of the treatments significantly enhanced this effect. After treatment withdrawal, all of the groups showed increases in nicotine Self-Administration, but only the combined treatment group remained significantly below control rates of nicotine Self-Administration. CONCLUSIONS: This study showed the promise of amitifadine as a possible new treatment for smoking cessation and suggested that amitifadine is more effective when given with chronic nicotine. The improved efficacy of the amitifadine and nicotine combination may be potentiated by amitifadine's inhibitory effects on CYP2B, which slows nicotine metabolism. IMPLICATIONS: This study replicated the effects that chronic nicotine or chronic amitifadine, a triple reuptake inhibitor, significantly reduces nicotine Self-Administration in rats. It extends those findings by showing that the combination of chronic nicotine plus amitifadine causes significantly greater reduction in nicotine Self-Administration than either drug treatment alone. The combination of chronic amitifadine and chronic nicotine also causes a persistent significant reduction in nicotine Self-Administration after the end of treatment. The amitifadine and nicotine treatment should be assessed in humans to determine whether this combination provides greater efficacy in smoking cessation than transdermal nicotine treatment alone.
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Threshold of adulthood for the onset of nicotine Self-Administration in male and female rats.
Behavioural brain research, 2011Co-Authors: Edward D. Levin, Susan Slade, Corinne Wells, Marty Cauley, Ann Petro, Analise Vendittelli, Michael A. Johnson, Paul Williams, Kofi Horton, Amir H. RezvaniAbstract:Abstract The great majority of tobacco addiction begins during adolescence. More heavily addicted smokers begin smoking earlier, but differentiating the neurobehavioral impact of nicotine Self-Administration during adolescence from self-selection bias (whereby people more prone to heavy addiction also begin earlier) cannot be ethically unconfounded in humans. The goals of this research were to determine the age threshold for the adult-like nicotine Self-Administration and determine sex differences. Male and female Sprague-Dawley rats were tested for nicotine Self-Administration starting at 4, 5, 6, 7, and 8 weeks of age in an operant FR1 schedule for IV nicotine (0.03 mg/kg/infusion) in 45-min sessions for 2 weeks, with 1 week of enforced abstinence and 1 week of resumed access. This study replicated our earlier work that nicotine Self-Administration was increased in adolescent vs. adult rats and that the effect was more pronounced in adolescent males, but the increased nicotine Self-Administration was more persistent in adolescent-onset females. The age threshold for adult-like behavior was 6–7 weeks of age. Adolescent-onset nicotine Self-Administration had persisting effects of eggaurated increases of nicotine Self-Administration when fixed-ratio requirements for Self-Administration were lowered. Female rats that had begun nicotine Self-Administration during adolescence showed exaggerated increases in nicotine Self-Administration after a switch back to FR1 from FR8, indicating a lessened control over their Self-Administration. Adolescent-onset nicotine Self-Administration was not found to potentiate cocaine Self-Administration. Adolescent-onset nicotine Self-Administration causes persistent increases in nicotine Self-Administration in female rats even after they reach adulthood and disrupts control over Self-Administration behavior.
Amir H. Rezvani - One of the best experts on this subject based on the ideXlab platform.
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Dextromethorphan and bupropion reduces high level remifentanil Self-Administration in rats.
Pharmacology biochemistry and behavior, 2020Co-Authors: Graham Blair, Corinne Wells, Amir H. Rezvani, John Modarres, Caroline Pace, James M. Davis, Jed E. Rose, Edward D. LevinAbstract:Abstract Opiate addiction has risen substantially during the past decade. New treatments to combat opiate addiction are sorely needed. The current study was conducted to determine the acute individual and interactive effects of bupropion and dextromethorphan in a rat model of opiate Self-Administration using the short-acting synthetic opioid remifentanil. Both of these drugs have been found to reduce Self-Administration of nicotine. Bupropion and dextromethorphan and their combination had differential effects depending on whether the rats showed higher or lower baseline remifentanil Self-Administration. The rats with higher initial remifentanil Self-Administration showed a significant decrease in remifentanil Self-Administration with bupropion or dextromethorphan treatment, compared to the vehicle control condition. This decrease in self-remifentanil administration was most pronounced when combination of the higher doses of bupropion and dextromethorphan were administered. In contrast, the rats with lower baseline remifentanil Self-Administration showed the opposite effect of drug treatment with an increase in remifentanil Self-Administration with bupropion treatment compared to the vehicle control condition. Dextromethorphan had no significant effect inthis group. This study shows that combination bupropion and dextromethorphan affects remifentanil Self-Administration in a complex fashion with differential effects on low and high baseline responders. In subjects with high baseline remifentanil Self-Administration, bupropion and dextromethorphan treatment significantly reduced Self-Administration, whereas in subjects with low baseline remifentanil Self-Administration, bupropion increased remifentanil Self-Administration and dextromethorphan had no discernible effect. This finding suggests that combination bupropion-dextromethorphan should be tested in humans, with a focus on treating people with high-level opiate use.
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Chronic memantine decreases nicotine Self-Administration in rats.
European journal of pharmacology, 2019Co-Authors: Edward D. Levin, Corinne Wells, Jed E. Rose, Leah Yao, Wendi Guo, Anica Nangia, Sarah Howard, Erica Pippen, Andrew B. Hawkey, Amir H. RezvaniAbstract:Neurobehavioral bases of tobacco addiction and nicotine reinforcement are complex, involving more than only nicotinic cholinergic or dopaminergic systems. Memantine is an NMDA glutamate antagonist used to improve cognitive function in people with Alzheimer's disease. Glutamate may be an important component of the reinforcing effects of nicotine, so memantine was evaluated as a potential smoking cessation aid. Two studies were conducted with adult female rats, one testing acute effects of memantine over a range of doses for changing nicotine Self-Administration and the other testing the chronic effects of memantine to reduce nicotine Self-Administration. Acute memantine injections slightly, but significantly, increased nicotine Self-Administration in a dose-related manner. In contrast, chronic memantine treatment significantly reduced nicotine Self-Administration. During the first day of memantine administration in the chronic study, nicotine Self-Administration was significantly elevated replicating the acute study. Starting in the second week of treatment there was a significant reduction of nicotine Self-Administration relative to controls. This was seen because memantine treatment prevented the increase in nicotine Self-Administration shown by controls. There even continued to be a memantine-induced lowered nicotine Self-Administration during the week after the cessation of memantine treatment. Memantine or other drugs affecting NMDA glutamate receptors may be useful aids to smoking cessation. Full efficacy for reducing nicotine Self-Administration was seen as the NMDA drug treatment is given chronically. Importantly, the effect persisted even after treatment is ended, indicating the high potential for NMDA glutamate receptors to impact nicotine addiction.
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Prolonging the Reduction of Nicotine Self-Administration in Rats by Coadministering Chronic Nicotine With Amitifadine, a Triple Monoamine Reuptake Inhibitor With CYP2B6 Inhibitory Actions.
Nicotine & Tobacco Research, 2019Co-Authors: Edward D. Levin, Susan Slade, Corinne Wells, Jed E. Rose, Anthony A Mckinney, Amir H. RezvaniAbstract:INTRODUCTION: Existing treatments can aid tobacco smoking cessation, but they have low efficacy. Because there is a network of neural systems involved in tobacco addiction, combination treatments may provide greater efficacy. Chronic nicotine and amitifadine have each been shown to significantly reduce nicotine Self-Administration in rats. This study was conducted to determine if the combination of chronic nicotine with amitifadine, a triple monoamine reuptake inhibitor with CYP2B inhibitory effects, would reduce nicotine Self-Administration to a greater extent than either alone or placebo. METHODS: This study tested the combination of nicotine plus amitifadine in young adult female Sprague-Dawley rats self-administering nicotine (0.03 mg/kg/infusion). This combination was compared with each treatment alone and the vehicle during continuing nicotine Self-Administration as well as during resumption of Self-Administration after a week of enforced abstinence, modeling a quit attempt. Finally, we studied the residual effects of these therapies after discontinuation of treatment. RESULTS: Treatment with either chronic nicotine or amitifadine alone significantly reduced nicotine Self-Administration relative to controls. The combination of the treatments significantly enhanced this effect. After treatment withdrawal, all of the groups showed increases in nicotine Self-Administration, but only the combined treatment group remained significantly below control rates of nicotine Self-Administration. CONCLUSIONS: This study showed the promise of amitifadine as a possible new treatment for smoking cessation and suggested that amitifadine is more effective when given with chronic nicotine. The improved efficacy of the amitifadine and nicotine combination may be potentiated by amitifadine's inhibitory effects on CYP2B, which slows nicotine metabolism. IMPLICATIONS: This study replicated the effects that chronic nicotine or chronic amitifadine, a triple reuptake inhibitor, significantly reduces nicotine Self-Administration in rats. It extends those findings by showing that the combination of chronic nicotine plus amitifadine causes significantly greater reduction in nicotine Self-Administration than either drug treatment alone. The combination of chronic amitifadine and chronic nicotine also causes a persistent significant reduction in nicotine Self-Administration after the end of treatment. The amitifadine and nicotine treatment should be assessed in humans to determine whether this combination provides greater efficacy in smoking cessation than transdermal nicotine treatment alone.
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Threshold of adulthood for the onset of nicotine Self-Administration in male and female rats.
Behavioural brain research, 2011Co-Authors: Edward D. Levin, Susan Slade, Corinne Wells, Marty Cauley, Ann Petro, Analise Vendittelli, Michael A. Johnson, Paul Williams, Kofi Horton, Amir H. RezvaniAbstract:Abstract The great majority of tobacco addiction begins during adolescence. More heavily addicted smokers begin smoking earlier, but differentiating the neurobehavioral impact of nicotine Self-Administration during adolescence from self-selection bias (whereby people more prone to heavy addiction also begin earlier) cannot be ethically unconfounded in humans. The goals of this research were to determine the age threshold for the adult-like nicotine Self-Administration and determine sex differences. Male and female Sprague-Dawley rats were tested for nicotine Self-Administration starting at 4, 5, 6, 7, and 8 weeks of age in an operant FR1 schedule for IV nicotine (0.03 mg/kg/infusion) in 45-min sessions for 2 weeks, with 1 week of enforced abstinence and 1 week of resumed access. This study replicated our earlier work that nicotine Self-Administration was increased in adolescent vs. adult rats and that the effect was more pronounced in adolescent males, but the increased nicotine Self-Administration was more persistent in adolescent-onset females. The age threshold for adult-like behavior was 6–7 weeks of age. Adolescent-onset nicotine Self-Administration had persisting effects of eggaurated increases of nicotine Self-Administration when fixed-ratio requirements for Self-Administration were lowered. Female rats that had begun nicotine Self-Administration during adolescence showed exaggerated increases in nicotine Self-Administration after a switch back to FR1 from FR8, indicating a lessened control over their Self-Administration. Adolescent-onset nicotine Self-Administration was not found to potentiate cocaine Self-Administration. Adolescent-onset nicotine Self-Administration causes persistent increases in nicotine Self-Administration in female rats even after they reach adulthood and disrupts control over Self-Administration behavior.
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Adolescent-onset nicotine Self-Administration modeled in female rats
Psychopharmacology, 2003Co-Authors: Edward D. Levin, Amir H. Rezvani, Jed E. Rose, Daniel Montoya, H. Scott SwartzwelderAbstract:Rationale Although the great majority of tobacco addiction begins during adolescence, little is known about differential nicotine effects in adolescents versus adults. Objectives A rat model was used to determine the impact of the age of onset on nicotine Self-Administration. Methods In expt 1, nicotine Self-Administration of female Sprague-Dawley rats over a range of acute doses (0.01–0.08 mg/kg per infusion) was determined in adolescent (beginning at 54–62 days) versus adult (beginning at 84–90 days). In expt 2, chronic nicotine Self-Administration over 4 weeks from adolescence into adulthood was compared with the chronic Self-Administration beginning in adulthood. In expt 3, adolescent-adult differences in nicotine effects on body temperature and locomotor responses were determined. Results Adolescent-onset rats showed a significant main effect of increased nicotine intake compared with adult-onset rats in an eight-fold range of acute unit doses/infusion. Significant age differences were also seen in the chronic level of nicotine Self-Administration. Over 4 weeks, the adolescent-onset group had nearly double the rate of nicotine Self-Administration of the benchmark nicotine dose (0.03 mg/kg per infusion) compared to the adult-onset group. This increased nicotine intake persisted into adulthood. Adolescent rats had significantly greater response than adults to the hypothermic effects of nicotine, but had significantly less response than adults to the reduction in locomotor activity seen after nicotine. Conclusions Adolescent-onset nicotine Self-Administration in female rats was associated with significantly higher levels of nicotine Self-Administration versus rats, which began nicotine Self-Administration in adulthood. This greater Self-Administration persists into adulthood and may underlie greater propensity of adolescents to nicotine addiction.
Roger D Spealman - One of the best experts on this subject based on the ideXlab platform.
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Intravenous Self-Administration of etonitazene alone and combined with cocaine in rhesus monkeys: comparison with heroin and antagonism by naltrexone and naloxonazine
Psychopharmacology, 2009Co-Authors: Cindy Achat-mendes, Glenn R. Valdez, Donna M. Platt, James K. Rowlett, Roger D SpealmanAbstract:Rationale In humans, μ opioid–cocaine combinations (speedballs) have been reported to heighten pleasurable effects and result in greater abuse potential compared to either drug individually. Emerging evidence in animals suggests that the ability of μ opioids to enhance the reinforcing effects of cocaine might be independent of their μ intrinsic efficacy even though μ agonist efficacy appears to be a determinant in the reinforcing effects of μ opioids themselves. Objectives This study examined the relationship between agonist efficacy, Self-Administration, and the enhancement of cocaine Self-Administration using the high-efficacy μ agonist etonitazene. Materials and methods Rhesus monkeys self-administered cocaine, heroin, etonitazene, and opioid–cocaine combinations under a progressive-ratio schedule of intravenous drug injection. Results Unlike cocaine and heroin, etonitazene did not maintain consistent Self-Administration at any dose tested (0.001–1.0 μg/kg/injection). However, combining etonitazene (0.1–1.0 μg/kg/injection) with cocaine (0.01 and 0.03 mg/kg/injection) enhanced cocaine Self-Administration, and this enhancement was attenuated by naltrexone. These effects are similar to those obtained by combining non-reinforcing doses of heroin and cocaine. Antagonism of etonitazene–cocaine and heroin–cocaine Self-Administration by naloxonazine was short lasting and was not maintained after 24 h (when naloxonazine’s purported μ_1 subtype antagonist effects are thought to predominate). Conclusions The results suggest that high μ agonist efficacy does not guarantee consistent drug Self-Administration and that the ability of μ agonists to enhance cocaine Self-Administration does not depend exclusively on reinforcing efficacy. Moreover, the results do not support a major role for μ_1 receptor mechanisms in either etonitazene- or heroin-induced enhancement of cocaine Self-Administration.
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Intravenous Self-Administration techniques in monkeys.
Current protocols in neuroscience, 2005Co-Authors: Donna M. Platt, Galen Carey, Roger D SpealmanAbstract:Drug Self-Administration is a procedure in which a subject performs a response, called an operant, that results in the delivery of a drug injection. This procedure is viewed as a relevant model for the study of human drug-taking behavior. Drug Self-Administration in primates has several characteristics that resemble drug-taking behavior in humans, and drugs that are commonly abused by humans also typically maintain Self-Administration behavior in monkeys. Drug Self-Administration procedures allow for the study of a variety of drug properties. For instance, they are used to investigate the abuse potential of new compounds and to study the effects of candidate medications for the treatment of drug addiction. These procedures also can be used to study the process of drug reinforcement. This unit describes intravenous drug Self-Administration in large primates, such as rhesus macaques, and smaller primates, such as squirrel monkeys.
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UNIT 10.5 Models of Neurological Disease (Substance Abuse): Self-Administration in Monkeys
Current protocols in pharmacology, 1998Co-Authors: Galen J Carey, Roger D SpealmanAbstract:Drug Self-Administration is a procedure in which a subject performs a specified response that results in the delivery of a drug injection. This procedure is viewed as a relevant model for the study of human drug-taking behavior. Drug Self-Administration in primates has several characteristics that resemble drug-taking behavior in humans, and agents commonly abused by humans also generally maintain Self-Administration behavior in monkeys. Self-Administration procedures allow for the study of a variety of drug properties. For instance, they can be used to investigate the abuse potential of new compounds and to study the effects of candidate medications for the treatment of drug addiction. These procedures can also be employed for examining drug reinforcement mechanisms. Described in this unit are procedures for studying intravenous drug Self-Administration in large primates, such as rhesus macaques, and smaller primates, such as squirrel monkeys. Curr. Protoc. Pharmacol. 56:10.5.1-10.5.17. © 2012 by John Wiley & Sons, Inc. Keywords: Self-Administration; monkey; intravenous
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Self-Administration of D1 receptor agonists by squirrel monkeys
Psychopharmacology, 1996Co-Authors: D. M. Grech, Roger D Spealman, Jack BergmanAbstract:Dopaminergic mechanisms are believed to play a prominent role in the Self-Administration of cocaine and other abused stimulants. The contribution of D2 receptors is now well established, but less is known about the role of D1 receptors in the reinforcing effects of these drugs. To help clarify the role of D1 mechanisms in stimulant Self-Administration, agonists differing in D1 receptor selectivity (SKF 81297>SKF 82958>SKF 77434) and efficacy (SKF 82958>SKF 81297>SKF 77434) were studied for their ability to maintain IV Self-Administration in squirrel monkeys previously trained to self-administer cocaine. Up to a 100-fold range of doses of each D1 agonist was studied under both a fixed-ratio (FR) and a second-order fixed-interval (FI) schedule of reinforcement. Parallel studies were conducted with the D2 receptor agonists, (+)-PHNO and quinpirole, under the second-order FI schedule. Of the three D1 agonists, only SKF 82958 maintained consistent Self-Administration under both the FR and second-order FI schedules and had dose-related effects that were qualitatively similar to those of (+)-PHNO and quinpirole under the latter condition. SKF 81297, which has high selectivity at D1 receptors and intermediate agonist efficacy, maintained Self-Administration in the majority of monkeys under the FR schedule, but did not maintain Self-Administration under the second-order FI schedule. SKF 77434, which has moderate selectivity at D1 receptors and low agonist efficacy, did not maintain Self-Administration under either schedule. The results suggest that the ability of D1 agonists to maintain IV Self-Administration in squirrel monkeys depends both on the type of schedule and on the pharmacological properties (i.e. selectivity and efficacy) of the particular drug. These results are also consistent with the view that D1, in addition to D2, receptor mechanisms play a role in the Self-Administration of abused stimulants.
